Cotrim(200 mg+40 mg)/5 ml

Cotrim is a fixed-dose combination antibacterial (sulfamethoxazole, a sulfonamide, plus trimethoprim, a dihydrofolate reductase inhibitor), commonly known as co-trimoxazole, used against a range of susceptible bacterial infections. Because the two components act sequentially on bacterial folic acid synthesis, Cotrim has a broader spectrum and lower resistance potential than either agent used alone.

Established / FDA-approved uses

• Acute, uncomplicated and complicated urinary tract infections (UTIs) caused by susceptible strains of common uropathogens.
• Acute otitis media in children (when caused by susceptible organisms and when first-line agents are unsuitable).
• Acute exacerbations of chronic bronchitis in adults caused by susceptible bacteria.
• Traveler's diarrhea in adults caused by susceptible strains of enterotoxigenic E. coli.
• Shigellosis (enteritis) caused by susceptible strains of Shigella.
• Treatment of, and primary and secondary prophylaxis against, Pneumocystis jirovecii pneumonia (PCP), particularly in immunocompromised patients such as those with HIV/AIDS.

Guideline-supported off-label uses

• Prophylaxis of toxoplasmosis in patients at high risk (e.g. advanced HIV disease), often used as an alternative regimen.
• Treatment of infections caused by Stenotrophomonas maltophilia and Nocardia species, where Cotrim is a preferred or alternative agent per infectious-disease guidelines.
• Treatment of mild-to-moderate skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus (MRSA), per some guidelines, usually as one option among several.

Cotrim should only be used for infections proven or strongly suspected to be caused by susceptible organisms; it is not effective against viral infections, and use should be guided by culture and sensitivity results where feasible.

Each tablet, dispersible tablet, oral suspension, or injectable formulation of Sulphamethoxazole + Trimethoprim contains sulfamethoxazole and trimethoprim in a fixed 5:1 ratio (for example, a standard tablet commonly contains 400 mg sulfamethoxazole with 80 mg trimethoprim, and a double-strength tablet 800 mg sulfamethoxazole with 160 mg trimethoprim; pediatric suspensions typically supply 200 mg sulfamethoxazole with 40 mg trimethoprim per 5 mL). Exact strength varies by product and dosage form; refer to the specific pack/label of the product dispensed.

Cotrim is a synthetic combination antibacterial agent that pairs sulfamethoxazole, a sulfonamide, with trimethoprim, a diaminopyrimidine, in a fixed ratio. The combination is often referred to as co-trimoxazole. Each component blocks a separate, sequential step in the bacterial folic acid synthesis pathway that bacteria need to make DNA and multiply; used together, they produce a synergistic, often bactericidal effect against a broad range of gram-positive and gram-negative bacteria that would not be achieved with either drug alone, while also reducing the likelihood that bacteria develop resistance during treatment.

Combination antibacterial (sulfonamide plus dihydrofolate reductase inhibitor); Cotrim belongs to the folate-pathway-inhibitor class of antimicrobials, commonly termed co-trimoxazole.

Sulphamethoxazole + Trimethoprim works through sequential inhibition of two enzymes in the bacterial folic acid synthesis pathway, which bacteria require to synthesize purines, pyrimidines, and ultimately DNA.

Sulfamethoxazole component

Sulfamethoxazole is a structural analog of para-aminobenzoic acid (PABA) that competitively inhibits dihydropteroate synthase, the bacterial enzyme responsible for incorporating PABA into dihydrofolic acid.

Trimethoprim component

Trimethoprim selectively inhibits bacterial dihydrofolate reductase, blocking the reduction of dihydrofolic acid to tetrahydrofolic acid (the active form of folate needed for nucleic acid synthesis), with much weaker affinity for the corresponding human enzyme.

By blocking two consecutive steps of the same pathway, Sulphamethoxazole + Trimethoprim produces a synergistic, often bactericidal effect against many gram-positive and gram-negative organisms, including several strains resistant to either agent alone, and this dual blockade also lowers the likelihood of bacteria developing resistance compared with single-agent sulfonamide or trimethoprim therapy.

Take Cotrim by mouth, generally with a full glass of water, with or without food (taking it with food may reduce stomach upset). For the oral suspension, shake well before each use and measure the dose with an accurate oral measuring device, not a household spoon. Drink plenty of fluids throughout the course to reduce the risk of crystalluria. If a dose is missed, take it as soon as remembered unless it is close to the time for the next dose, in which case skip the missed dose; do not double up doses. Complete the full course as prescribed, even if you feel better, and do not stop, extend, skip doses, or share Cotrim with others without medical advice.

Cotrim has the following well-verified, clinically significant drug interactions:

• Warfarin and other oral anticoagulants: Cotrim can markedly potentiate anticoagulant effect (by displacing warfarin from protein binding and inhibiting its metabolism), increasing bleeding risk; monitor INR closely and adjust anticoagulant dose if co-administered.
• ACE inhibitors, angiotensin receptor blockers (ARBs), potassium-sparing diuretics, and other potassium-elevating drugs: the trimethoprim component can cause hyperkalemia, especially in elderly patients or those with renal impairment; this risk is increased with concurrent use, and potassium levels should be monitored.
• Methotrexate: Cotrim can increase free methotrexate levels and add to antifolate toxicity (bone marrow suppression); concurrent use requires caution and monitoring, or avoidance.
• Phenytoin: Cotrim inhibits phenytoin metabolism, increasing phenytoin levels and toxicity risk; monitor phenytoin levels if co-administered.
• Sulfonylurea oral hypoglycemics (e.g. glipizide, glyburide): Cotrim can potentiate hypoglycemic effect; monitor blood glucose.
• Digoxin: Cotrim may increase serum digoxin concentration, particularly in elderly patients; monitor digoxin levels.
• Cyclosporine: concurrent use may increase risk of nephrotoxicity and reduce cyclosporine levels in transplant patients; renal function should be monitored.

Inform your physician or pharmacist of all other medicines, supplements, and herbal products you are taking before starting Cotrim.

Side effects of Cotrim include:

Common side effects

• Nausea, vomiting, loss of appetite, diarrhea
• Headache
• Skin rash

Less common but important side effects

• Severe hypersensitivity reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis - stop Cotrim immediately and seek urgent medical attention for any rash, blistering, or mucosal (mouth/eye/genital) involvement
• Hyperkalemia, particularly in the elderly, those with renal impairment, or those on interacting drugs (see Interactions)
• Blood dyscrasias with prolonged use (leukopenia, thrombocytopenia, agranulocytosis, aplastic anemia) - rare, monitor with extended courses
• Photosensitivity (increased sunburn risk)
• Elevated liver enzymes, hepatitis (rare)
• Crystalluria, and rarely acute kidney injury, if fluid intake is inadequate

Report any rash, unusual bruising/bleeding, jaundice, or persistent/severe side effects from Cotrim to your physician promptly.

Cotrim should generally be avoided during pregnancy, particularly in the first trimester, because folate antagonism has been associated with an increased risk of neural tube and other birth defects, and it should also be avoided at term/near delivery because of the risk of neonatal kernicalus (kernicterus) from displacement of bilirubin. If treatment is considered necessary during pregnancy, Cotrim should be used only if clearly needed, no safer alternative is suitable, and the potential benefit justifies the potential risk to the fetus, under close medical supervision and with folate supplementation as advised by the physician.

Both components of Cotrim pass into breast milk. Because of the risk of kernicterus and hemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient infants, Cotrim is generally avoided during breastfeeding, especially with infants who are premature, jaundiced, ill, or G6PD-deficient; use only if clearly needed and a physician has weighed the benefits and risks.

Use Cotrim with the following precautions:

• Antibiotic stewardship: take Cotrim exactly as prescribed by your physician; do not stop, extend, skip doses, or share this medicine with others without medical advice, to reduce the risk of resistance and relapse.
• Severe skin reactions: discontinue Cotrim immediately and seek medical attention at the first sign of rash, blistering, or mucosal involvement, which may indicate Stevens-Johnson syndrome or toxic epidermal necrolysis.
• Hyperkalemia: use with caution and monitor potassium in the elderly, patients with renal impairment, and those taking ACE inhibitors, ARBs, or potassium-sparing diuretics.
• Blood disorders: use with caution in patients with pre-existing blood dyscrasias or folate deficiency; periodic blood counts are advisable with prolonged courses.
• G6PD deficiency: may precipitate hemolytic anemia in G6PD-deficient patients; use with caution.
• Renal or hepatic impairment: use with caution and appropriate dose adjustment; avoid in severe impairment (see Contraindications).
• Photosensitivity: avoid excessive sun/UV exposure and use sun protection during treatment.
• Adequate hydration: maintain good fluid intake during treatment to reduce the risk of crystalluria.
• Superinfection: prolonged use may result in overgrowth of non-susceptible organisms, including Clostridioides difficile-associated diarrhea.

Overdose of Cotrim may cause nausea, vomiting, abdominal pain, drowsiness, confusion, and, with significant overdose, bone marrow suppression, jaundice, and crystalluria may occur. If overdose of Cotrim is suspected, seek immediate medical attention or contact a poison control center/emergency services; do not attempt to manage a suspected overdose at home. Treatment is supportive and may include gastric decontamination if presenting early, and folinic acid may be given by a physician to counteract bone-marrow toxicity from the trimethoprim component.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children. Do not use after the expiry date printed on the pack.

Elderly: use Cotrim with caution in elderly patients, who are at higher risk of severe adverse effects such as hyperkalemia, severe skin reactions, and blood dyscrasias; renal function should be assessed before and during treatment.

Pediatric patients: Cotrim is contraindicated in infants younger than 2 months of age. In older infants and children, it is used at weight-based doses for approved indications (see Pediatric Uses).

Renal impairment: dose reduction is required when creatinine clearance is 15-30 mL/min; use is generally avoided below 15 mL/min unless hemodialysis is available (see Dosage and Administration).

Hepatic impairment: use with caution in mild-moderate impairment; avoid in severe hepatic damage (see Contraindications).

Pregnancy and breastfeeding: see Pregnancy and Lactation.

G6PD deficiency: use with caution due to risk of hemolytic anemia.

The duration of treatment with Cotrim depends on the indication: typically 5 days for traveler's diarrhea, 10-14 days for urinary tract infections and acute bronchitis exacerbations, 10 days for acute otitis media, and 14-21 days for treatment of Pneumocystis jirovecii pneumonia. When used for PCP prophylaxis, treatment is often continued long-term as directed by a physician, based on the patient's underlying immune status. Always complete the full course prescribed and do not stop early even if symptoms improve.

Sulfonamide antibacterial (sulfamethoxazole) combined with a dihydrofolate reductase inhibitor (trimethoprim); Sulphamethoxazole + Trimethoprim is classified as a folate-pathway-inhibiting combination antimicrobial (co-trimoxazole).

Sulphamethoxazole + Trimethoprim acts through sequential blockade of bacterial folic acid synthesis. The sulfamethoxazole component competitively inhibits dihydropteroate synthase, preventing incorporation of para-aminobenzoic acid (PABA) into dihydrofolic acid, while the trimethoprim component inhibits bacterial dihydrofolate reductase, blocking conversion of dihydrofolic acid to the active tetrahydrofolic acid needed for purine, pyrimidine, and ultimately DNA synthesis. Because the two agents act at consecutive steps of the same pathway with a high degree of selectivity for bacterial over human enzymes, their combination produces a synergistic, often bactericidal effect against a broad range of susceptible gram-positive and gram-negative bacteria.

Category C (Category D at term, near delivery)

Cotrim is contraindicated in infants younger than 2 months of age because of the risk of displacing bilirubin and precipitating kernicterus, and because of general concerns about sulfonamide use in this age group. In children older than 2 months, Cotrim is approved for use in urinary tract infections, acute otitis media, and shigellosis, dosed on a weight basis according to the trimethoprim component, and it is also used, under specialist supervision, for the treatment and prophylaxis of Pneumocystis jirovecii pneumonia in children at risk (e.g. those with HIV infection or other immunocompromising conditions). Pediatric dosing must always be individualized and supervised by a physician, with attention to hydration, renal function, and monitoring for rash or blood count changes.